中国肿瘤生物治疗杂志2011，Vol.18Issue(4)：373-377,5.DOI:10.3872/j.issn.1007-385X.2011.04.006
5/35嵌合型溶瘤腺病毒SG635对肝癌细胞的抑制作用
Inhibitory effect of 5/35 chimeric oncolytic adenovirus SG635 on hepatocarcinoma cells
摘要
Abstract
Objective:To investigate the specific cytotoxicity effect of 5/35 chimeric oncolytic adenovirus SG635 on hepatocellular carcinoma HepG2 and SMMC-7721 cells. Methods; The knob and shaft domains of type 5 adenovirus ( Ad5 ) in SG600 plasmid were replaced by the domains of type 35 adenovirus ( Ad35 ) , and chimeric oncolytic adenovirus Ad5/35 was established. Flow cytometry was used to examine the infection efficiency of chimeric adenovirus Ad5/35 ( Ad5/35-EGFP) in HepG2 and SMMC-7721 cells; replication assay was used to evaluate the replication of oncolytic adenovirus SG635; Western blotting analysis was used to examine the expression of El A in cells after SG635 infection; and Kit-8 assay was used to assess the cytotoxicity of SG635 and SG600 on HepG2 and SMMC-7721 cells. Results; The infection efficiency of Ad5/35-EGFP in HepG2 and SMMC-7721 cells was obviously enhanced compared with Ad5-EGFP. The replication activity of SG635 in HepG2 and SMMC-7721 cells was higher than that of SG600 72 h after infection(15 848.93, 6 309.57 vs 6 309.57, 5 011.87, P＜0.01), but SG635 did not replicate in normal BJ cells. Moreover, SG635 induced a higher expression of El A protein in HepG2 and SMMC-7721 cells than SG600, but did not induce E1 A expression in normal BJ cells. At a certain MOI, SG635 showed increasing cytotoxieity on HepG2 (MOI = 1, 90% vs 60% ) and SMMC-7721 ( MOI = 10, 90% vs 50% ) cells, and the cytotoxieity was stronger than SG600, without causing significant cytotoxieity on normal BJ cells. Conclusion: The 5/35 chimeric oncolytic adenovirus SG635 can effectively infect and specifically kill hepatocarcinoma cells with satisfactory safety and specificity.关键词
溶瘤腺病毒/肝癌/病毒治疗/E1A蛋白Key words
oncolytic adenovirus/ hepatocellular carcinoma/ viral therapy/ E1 A protein分类
医药卫生引用本文复制引用
武玉强,张琪,陈伟,刘炜,台艳,陈规划..5/35嵌合型溶瘤腺病毒SG635对肝癌细胞的抑制作用[J].中国肿瘤生物治疗杂志,2011,18(4):373-377,5.基金项目
“十一五”国家科技重大专项课题资助项目(No.2008ZX10002-025,No.2008ZX10002-026) （No.2008ZX10002-025,No.2008ZX10002-026）
国家重点基础研究发展计划(973计划)资助项目(No.2009CB522404):教育部新世纪优秀人才基金资助项目(No.NCET-08-0583) （973计划）
全国优秀博士论文专项基金资助项目(No.FANEDD 200774) . （No.FANEDD 200774）
